Over ninety somatic cell hybrids between FeLV producing cat cells and endogenous MuLV producing mouse cells were examined for restriction of expression of Type C viruses and their structural proteins. The hybrids were highly segregated for feline chromosomes and retained the entire mouse chromosome complement as determined by karyological examination and development of 28 isozyme markers. All the hybrids were negative for FeLV and FeLV p27 and two were positive for RD114 and RD114 p30. All the hybrids were severely restricted in expression of a B-trophic endogenous virus seen in the mouse parent. Back selected experiments demonstrate a syntectic relationship between the feline MuLV restriction locus, glucose-6-phosphate dehydrogenase and hypoxanthine quanine phosphoriboxyl transferase. The block of the feline restriction locus occurs at a time late in virus maturation insofar as restricted hybrids form MuLV antigens and budding viruses but fail to release them into the culture medium. Twenty-two early passage tissue culture explants of methocholanthrine induced fibrosarcomas were examined electrophoretically for changes in 50 different proteins (21 major soluble proteins and 29 enzymes) reflecting dysfunction in the processes of gene action leading to a normal protein. The results suggest high degree of fidelity of overall gene action in transformed cells.